The principle objective of this proposal is to develop a high resolution, high detection efficiency positron emission tomography (PET) detector with depth-of-interaction (DOI) positioning that will also support multi-modality imaging (e.g., PET/MR). This detector design can be scaled to support imaging applications from mice to man. The key design features of this PET detector are the use of trapezoidal, salt crystals (TSC) and a maximum likelihood positioning method that we call statistics based positioning (SBP). In addition to the unique crystal geometry, the design will utilize silicon photomultiplier (SiPM) arrays. SiPMs are Geiger-mode avalanche photodiode devices that have very attractive performance characteristics for PET detectors, especially for PET-MR applications. In this R21 proposal, we will investigate a design tailored for small animal PET imaging. The design will support <0.8 mm image resolution and >15% absolute detection efficiency. It is envisioned that the detectors developed under this proposal will eventually be used to fabricate a very compact PET detector ring that will be compatible with operation in high field (e.g., >4.7T) MR systems. For this prototype work the TSC PET detector dimensions will be designed for a system inner ring diameter of ~6.0 cm. This diameter will support dedicated PET and PET/MR whole body mouse and rat brain imaging. The net result of this work is the development and evaluation of a new PET detector design that will provide state of the art imaging performance capabilities and that can be used as part of a compact, stand alone PET system or as part of a multi-modality imaging system (e.g., PET/MR). We believe that this design will provide an outstanding balance between performance and cost and that the design will be translatable to commercial adaptation. This proposal builds upon the previous work of the investigators developing high resolution discrete crystal PET detectors and high resolution monolithic crystal PET detectors. This new design synergistically brings together the inherent strengths of both methods, that is, modularity and excellent spatial resolution control (discrete crystals) and lower fabrication costs and inherent DOI positioning capability using single-sided readout (continuous crystals). The design is scalable to support ultra-high resolution small animal imaging; high resolution organ specific imaging; and whole-body PET imaging. In addition, this project will add to the knowledge based on how to optimize the use of SiPM devices for nuclear medicine imaging detector applications. Two specific areas in which this work will contribute are developing SiPM signal multiplexing techniques to optimize performance versus cost and developing temperature control strategies and temperature/gain dependent calibration procedures for SiPM devices.